Biaryl heterocyclic compounds and methods of making and using the same

Abstract

The present invention relates generally to the field of anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. More particularly, the invention relates to a family of compounds having both a biaryl moiety and at least one heterocylic moiety that are useful as such agents.

1. A compound having the structure 
       
         
           
           
               
               
           
         
       
     
     
       2. A tautomer of a compound having the structure 
       
         
           
           
               
               
           
         
       
     
     
       3. A pharmaceutically acceptable salt of a compound having the structure 
       
         
           
           
               
               
           
         
       
     
     
       4. The salt of  claim 3 , wherein the salt is a non-toxic inorganic or organic acid salt of a compound having the structure 
       
         
           
           
               
               
           
         
       
     
     
       5. The salt of  claim 4 , wherein the nontoxic inorganic or organic acid is selected from 2-acetoxybenzoic, 2-hydroxyethane sulfonic, acetic, ascorbic, benzene sulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methane sulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicyclic, stearic, subacetic, succinic, sulfamic, sutfanilic, sulfuric, tannic, tartaric, and toluene sulfonic. 
     
     
       6. The salt of  claim 4 , wherein the acid is hydrochloric. 
     
     
       7. A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
       8. A pharmaceutical composition comprising the tautomer of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
       9. A pharmaceutical composition comprising the salt of  claim 3  and a pharmaceutically acceptable carrier. 
     
     
       10. A method of ameliorating a symptom of a microbial infection in a mammal comprising the step of administering to the mammal an effective amount of a compound or composition according to any one of  claims 1 - 9 . 
     
     
       11. The method according to  claim 10 , wherein the compound is administered orally, parentally, or topically. 
     
     
       12. A method of ameliorating a symptom of a disorder in a mammal comprising the step of administering to the mammal an effective amount of a compound or composition according to any one of  claims 1 - 9  wherein the disorder is selected from the group consisting of: a skin infection, nosocomial pneumonia, post-viral pneumonia, an abdominal infection, a urinary tract infection, bacteremia, septicemia, endocarditis, an atrio-ventricular shunt infection, a vascular access infection, meningitis, a peritoneal infection, a bone infection, a joint infection, a methicillin-resistant  Staphylococcus aurens  infection, a vancomycin-resistant  Enterococci  infection, a linezolid-resistant organism infection, and tuberculosis. 
     
     
       13. The method according to  claim 12 , wherein the compound is administered orally, parentally, or topically. 
     
     
       14. A method of ameliorating a symptom of microbial infection in a mammal by administering to the mammal prior to undergoing a surgical procedure an effective amount of a compound or composition according to any one of  claims 1 - 9 .